194918-80-4Relevant articles and documents
Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: New tools to discriminate between metabotropic glutamate receptor subtypes
Acher, Francine C.,Tellier, Frédérique J.,Azerad, Robert,Brabet, Isabelle N.,Fagni, Laurent,Pin, Jean R.
, p. 3119 - 3129 (1997)
The four stereoisomers of 1-aminocyclopentane-1,3,4-tricarboxylic acid {ACPT-I (18) and -II (19), (3R,4R)-III [(-)-20], and (3S,4S)-III [(+)-20]} have been synthesized and evaluated for their effects at glutamate receptors subtypes. ACPTs are ACPD analogues in which a third carboxylic group has been added at position 4 in the cyclopentane ring. None of the ACPT isomers showed a significant effect on ionotropic NMDA, KA, and AMPA receptors. On the other hand, ACPT-III (19) was found to be a general competitive antagonist for metabotropic receptors (mGluRs) and exhibited a similar affinity for mGluR1a (K(B) = 115 ± 2 μM), mGluR2 (K(B) = 88 ± 21 μM), and mGluR4a (K(B) = 77 ± 9 μM), the representative members of group I, II and III mGluRs, respectively. Two other isomers, ACPT-I (18) and (+)-(3S,4S)-ACPT-III [(+)- 20], were potent agonist at the group III receptors mGluR4a (EC50 = 7.2 ± 2.3 and 8.8 ± 3.2 μM) and competitive antagonists with low affinity for mGluR1a and mGluR2 (K(B) > 300 μM). Finally, (-)-(3R,4R)-ACPT-III [(-)-20] was a competitive antagonist with poor but significant affinity for mGluR4a (K(B) = 220 μM). These results demonstrate that the addition of a third carboxylic group to ACPD can change its activity (from agonist to antagonist) and either increase or decrease its selectivity and/or affinity for the various mGluR subtypes.
